Previous studies have shown that, of the six possible methylchrysene isomers, only 5-methylchrysene is carcinogenic in the experimental animal, and it is one of the most active known chemical carcinogens. This observation affords a unique opportunity for the study of structure-activity relationships in polynuclear aromatic hydrocarbons (PAH) and opens the door to an understanding of the molecular events which lead to cancer following the introduction of certain PAH into biological systems. Our objective is to determine the particular molecular characteristics in the methylchrysens system which result in carcinogenicity. We shall accomplish this by studying the effects of molecular geometry, substitution patterns, and the electronic distribution in the aromatic system, and metabolism to carcinogenic intermediates and to detoxified intermediates. Our specific objectives are the synthesis and bioassay of components related to carcinogenic 5- methylchrysene and non-carcinogenic 4-methylchrysene, a complete study of the metabolism of 4-methylchrysene and 5-methylchrysene to corroborate the conclusions reached from our bioassays regarding the most likely sites of interaction between chrysenes and cellular constituents, and determination of the x-ray crystal structure of 5- methylchrysene and 6-methylchrysene to give precise data on the influence of molecular geometry on carcinogenicity.